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Journal ArticleDOI

Quinone chemistry and toxicity

About: This article is published in Toxicology and Applied Pharmacology.The article was published on 1992-01-01. It has received 709 citations till now. The article focuses on the topics: Quinone.
Citations
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Journal ArticleDOI
TL;DR: The studies demonstrate that the increased biological potency of UFPs is related to the content of redox cycling organic chemicals and their ability to damage mitochondria.
Abstract: The objectives of this study were to determine whether differences in the size and composition of coarse (2.5-10 micro m), fine (< 2.5 microm), and ultrafine (< 0.1 microm) particulate matter (PM) are related to their uptake in macrophages and epithelial cells and their ability to induce oxidative stress. The premise for this study is the increasing awareness that various PM components induce pulmonary inflammation through the generation of oxidative stress. Coarse, fine, and ultrafine particles (UFPs) were collected by ambient particle concentrators in the Los Angeles basin in California and used to study their chemical composition in parallel with assays for generation of reactive oxygen species (ROS) and ability to induce oxidative stress in macrophages and epithelial cells. UFPs were most potent toward inducing cellular heme oxygenase-1 (HO-1) expression and depleting intracellular glutathione. HO-1 expression, a sensitive marker for oxidative stress, is directly correlated with the high organic carbon and polycyclic aromatic hydrocarbon (PAH) content of UFPs. The dithiothreitol (DTT) assay, a quantitative measure of in vitro ROS formation, was correlated with PAH content and HO-1 expression. UFPs also had the highest ROS activity in the DTT assay. Because the small size of UFPs allows better tissue penetration, we used electron microscopy to study subcellular localization. UFPs and, to a lesser extent, fine particles, localize in mitochondria, where they induce major structural damage. This may contribute to oxidative stress. Our studies demonstrate that the increased biological potency of UFPs is related to the content of redox cycling organic chemicals and their ability to damage mitochondria.

1,933 citations


Cites background from "Quinone chemistry and toxicity"

  • ...Quinones present in PM can act as catalysts to produce ROS directly and may be key compounds in PM-based oxidative stress (Monks et al. 1992; Penning et al. 1999)....

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Journal ArticleDOI
TL;DR: The mechanism by which quercetin may operate as an antioxidant as well as the potential use of this antioxidant as a nutraceutical (tested both ex vivo and in vivo) will be discussed.

1,598 citations


Cites background from "Quinone chemistry and toxicity"

  • ...It has been well described that oxidation products like semiquinone radicals and quinones display various toxic effects due to their ability of arylating protein thiols (Kalyanaraman et al., 1987; Ito et al., 1988; Monks et al., 1992; Metodiewa et al., 1999)....

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Journal ArticleDOI
TL;DR: The evidence strongly suggests that the numerous mechanisms of quinone toxicity can be correlated with the known pathology of the parent compound(s), including benzene, polycyclic aromatic hydrocarbons, estrogens, and catecholamines.
Abstract: Quinones represent a class of toxicological intermediates which can create a variety of hazardous effects in vivo, including acute cytotoxicity, immunotoxicity, and carcinogenesis. The mechanisms by which quinones cause these effects can be quite complex. Quinones are Michael acceptors, and cellular damage can occur through alkylation of crucial cellular proteins and/or DNA. Alternatively, quinones are highly redox active molecules which can redox cycle with their semiquinone radicals, leading to formation of reactive oxygen species (ROS), including superoxide, hydrogen peroxide, and ultimately the hydroxyl radical. Production of ROS can cause severe oxidative stress within cells through the formation of oxidized cellular macromolecules, including lipids, proteins, and DNA. Formation of oxidatively damaged bases such as 8-oxodeoxyguanosine has been associated with aging and carcinogenesis. Furthermore, ROS can activate a number of signaling pathways, including protein kinase C and RAS. This review explore...

1,499 citations

Journal ArticleDOI
TL;DR: This review discusses cellular sources of various radical species and their reactions with vital cellular constituents to provide insights into the controversy over whether free radicals are important mediators of tissue injury.
Abstract: A radical is any molecule that contains one or more unpaired electrons. Radicals are normally generated in many metabolic pathways. Some of these radicals can exist in a free form and subsequently interact with various tissue components resulting in dysfunction. The potential role of oxygen- or xenobiotic-derived free radicals in the pathology of several human diseases has stimulated extensive research linking the toxicity of numerous xenobiotics and disease processes to a free radical mechanism. However, because free radical-mediated changes are pervasive and often poorly understood, the question of whether such species are a major cause of tissue injury and human disease remains equivocal. This review discusses cellular sources of various radical species and their reactions with vital cellular constituents. Examples of purported free radical-mediated disorders are discussed in detail to provide insights into the controversy over whether free radicals are important mediators of tissue injury.

1,429 citations

Journal ArticleDOI
TL;DR: Proanthocyanidins (syn condensed tannins) are complex flavonoid polymers naturally present in cereals, legume seeds and particularly abundant in some fruits and fruit juices as mentioned in this paper.
Abstract: Proanthocyanidins (syn condensed tannins) are complex flavonoid polymers naturally present in cereals, legume seeds and particularly abundant in some fruits and fruit juices. They share some common structural features—phenolic nature and high molecular weight—with phenolic polymers found in black tea and red wine (called here tannin-like compounds). The polymeric nature of proanthocyanidins makes their analysis and estimation in food difficult. For this reason, little is known about their consumption, although they likely contribute a large part of the daily polyphenol intake. They also share common physicochemical properties: they form stable complexes with metal ions and with proteins and are, like other polyphenols, good reducing agents. Many of their biological effects of nutritional interest derive from these properties. As metal ion chelators, they influence the bioavailability of several minerals. The nutritional significance of the non-specific complexation of proteins is less clear. As reducing agents, they may participate in the prevention of cancers, both of the digestive tract and inner organs. They may also protect LDLs against oxidation and inhibit platelet aggregation and therefore prevent cardiovascular diseases. In vitro, animal and human studies on the prevention of these chronic diseases are reviewed with particular attention to wine and tea polyphenols. The lack of data on their bioavailability and the paucity of human studies are emphasised. © 2000 Society of Chemical Industry

1,199 citations

References
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Journal Article
Doyle G. Graham1
TL;DR: The autoxidation, periodate oxidation, and tyrosinase-mediated oxidation of 6-hydroxydopamine, dopamine, norepinephrine, and epinephrine were studied by absorption spectroscopy and gave evidence for a transient intermediate, the o -quinone, which rapidly tautomerized to the p-quinone.
Abstract: The autoxidation, periodate oxidation, and tyrosinase-mediated oxidation of 6-hydroxydopamine, dopamine, norepinephrine, and epinephrine were studied by absorption spectroscopy. Autoxidation and tyrosinase-mediated oxidation of the three catecholamines resulted in dopachrome analogues—aminochrome from dopamine, noradrenochrome from norepinephrine, and adrenochrome from epinephrine—without evidence for the expected intermediates, the o-quinones and the corresponding leukochromes. The use of periodate as an oxidant, on the other hand, allowed visualization of the o-quinone intermediates and the subsequent conversion to the dopachrome analogues. Cyclization of the o-quinones appeared to occur in the order epinephrine > norepinephrine > dopamine, while the rate of autoxidation occurred in the reverse order. The oxidation of 6-hydroxydopamine to its p-quinone was visualized under all three oxidizing conditions. However, the oxidation of 6-hydroxydopamine by periodate gave evidence for a transient intermediate, the o-quinone, which rapidly tautomerized to the p-quinone. The p-quinone product of 6-hydroxydopamine was seen to undergo cyclization to aminochrome, with subsequent polymerization.

1,161 citations

Book ChapterDOI
TL;DR: The knowledge of the way in which mutagens and carcinogens are metabolized is essential to a better understanding of their mode of action and of the processes for their detoxication.
Abstract: Publisher Summary This chapter discusses the role of glutathione (GSH) and glutathione s-transferases in metabolism of chemical carcinogens and other electrophilic agents. GSH is a tripeptide (I) that is present in nearly all living cells and is the most abundant sulfhydryl compound present in animal tissues, mainly in the cytosol. The chapter illustrates the wide range of electrophilic agents, including several known mutagens and carcinogens, which conjugate with GSH, a process usually catalyzed by the GSH S-transferases. This conjugation is probably a protective mechanism and is the initial stage in mercapturic acid biosynthesis for the elimination of foreign compounds from the body. GSH S-transferases provide protection not only by catalyzing the conjugation of a potential toxicant with GSH, but also by preferentially binding, even covalently, that toxicant. The reactive electrophiles that conjugate with GSH also bind to DNA, RNA, and protein and identification of GSH conjugates provide information on the nature of these biologically active intermediates or even their immediate precursors. Thus, the knowledge of the way in which mutagens and carcinogens are metabolized is essential to a better understanding of their mode of action and of the processes for their detoxication.

1,124 citations

Journal Article
TL;DR: 6-hydroxydopamine and 2,4,5-trihydroxyphenylalanine kill cells through the production of H2O2, O2[unknown], and OH·, while for dopamine and dopa the reaction of quinone oxidation products with nucleophiles probably also contributes to their cytotoxicity.
Abstract: The mechanism of cytotoxicity of 6-hydroxydopamine, 2,4,5-trihydroxyphenylalanine, dopa, dopamine, norepinephrine, and epinephrine was explored by asking whether cytotoxicity was a reflection of the potential for autoxidation of each polyphenol or of the sulfhydryl reactivity of its quinone products. The cytotoxicity of the polyphenols, as measured by inhibition of [3H]thymidine incorporation into DNA by C1300 neuroblastoma cells in tissue culture, correlated with the rate of autoxidation, as measured spectrophotometrically or by oxygen electrode studies. Polarographic determinations of the oxidation potentials of the polyphenols were also predictive of cytotoxicity; the most cytotoxic compounds had the most negative half-wave potentials and thus were the most readily oxidized. By contrast, the sulfhydryl reactivity of the quinone oxidation products of the polyphenols, as measured by inhibition of purified calf thymus DNA polymerase α, exhibited an inverse relationship to the cytotoxicity of the polyphenols; the most toxic compounds, 6-hydroxydopamine and 2,4,5-trihydroxyphenylalanine, were oxidized to the least reactive quinone products. An alternative mechanism of toxicity was observed with N -acetyldopamine, which was oxidized to 4-(2- N -acetylaminoethyl)-1,2-benzoquinone, a potent sulfhydryl reagent. N -Acetyldopamine was more toxic than predicted by its half-wave potential or its rate of autoxidation. Furthermore, while norepinephrine completely neutralized 6-hydroxydopamine and 2,4,5-trihydroxyphenylalanine as cytotoxic agents, the toxicity of N -acetyldopamine was minimally affected. Thus we conclude that 6-hydroxydopamine and 2,4,5-trihydroxyphenylalanine kill cells through the production of H2O2, O2[unknown], and OH·, while for dopamine and dopa the reaction of quinone oxidation products with nucleophiles probably also contributes to their cytotoxicity.

969 citations

Journal ArticleDOI
TL;DR: In the presence of cytotoxic concentrations of menadione rapid changes in intracellular thiol and Ca2+ homeostasis were observed and were associated with alterations in the surface structure of the hepatocytes which may be an early indication of cytOToxicity.

882 citations